Objective To observe the association between the red cell distribution width (RDW)/albumin (ALB) ratio (RAR) and the progression of diabetic retinopathy (DR). MethodsA cohort study. From June 2020 to February 2022, 835 diabetic patients who participated in the Phase II Beichen Eye Study, conducted at the Tianjin Medical University Eye Hospital were included. All participants underwent a two-year follow-up. Data were collected from patients at both baseline and the two-year follow-up, including mydriatic color fundus photography and laboratory tests for RDW and ALB. The RAR was calculated based on these measurements. DR was diagnosed and graded according to the DR International Clinical Severity Scale. Based on the progression of DR, patients were categorized into a non-progression group (689 cases, 83%) and a progression group (146 cases, 17%). Univariate models, as well as models Ⅰ, Ⅱ, and Ⅲ, were constructed after adjusting for various variables. The associations between RAR and its tertiles with the progression of DR were analyzed utilizing multivariate logistic regression analysis. Additionally, subgroup and interaction analyses were conducted to further investigate the relationship. ResultsThere was no significant difference in RDW and ALB levels between patients in the non-progression group and those in the progression group (t=-1.399, 1.954; P > 0.05). However, a significant difference was observed in RAR (t=-2.147, P=0.033). Results from the multivariate logistic regression analysis indicated that, in the fully adjusted model Ⅲ, RAR was an independent risk factor for the progression of DR. Specifically, each unit increase in RAR was associated with a 2.33-fold higher risk of DR progression [odds ratio (OR)= 2.33, 95% confidence interval (CI) 1.20-4.54, P = 0.013]. Compared to the univariate model, the predictive power of the fully adjusted model III for DR progression was 71.3% (area under the curve= 0.713, P < 0.001). Interaction analysis revealed a statistically significant difference in the effect of insulin use on the association between RAR and DR progression (insulin users: OR= 5.83, 95% CI 2.15-15.78, P=0.013). ConclusionsIncreased RAR is associated with a heightened risk of DR progression, and insulin use may influence the relationship between the two.